The following description of the background of the invention and references cited therein are not admitted to be prior art to the present invention.
Papillomaviruses are small DNA viruses. These viruses are associated with and/or thought to be the causative agent of a range of benign conditions (including benign lesions and benign tumors). Papillomaviruses have also been associated with malignancies such as squamous cell carcinoma in patients having the autosomal disease epidermodysplasia verricruciformis, and with genital cancers in both males and females.
There have now been at least 59 different types of HPV characterized, (see Manual of Clinical Microbiology; 998-1000; 5th ed. American Soc. for Microbiol. 1991). The genome of different HPV variants appears to be similar between all types (Van Ranst et al., J. Gen. Vir., 73:2653-60, 1992). Nonetheless, HPVs have been subject to differential typing, based on differences in the DNA sequences of different strains of the virus (Id.).
Among those HPV types associated with genital cancers are HPV types 16, 18, 31, 33 and 35. These five strains collectively are found in over 80% of all cervical tumors, suggesting a causative role.
Antigen detection of HPV types 16 and 18 has been described, but it is reported that commercially available sera react with antigens shared by all papillomaviruses (Roman and Fife, Clin. Microbiol. Rev. 2:166-190, 1989). In addition, the percentage of antigen-positive specimens is reported to decrease as the severity of the disease increases from mild dysplasia to carcinoma in situ, to invasive carcinoma (Id.).
In vivo, HPV DNA is found both episomally and integrated in the host genome. The HPV genome contains open reading frames encoding from 8 to 10 proteins, although not all of these proteins have been identified. Many of these open reading frames have been designated with the prefixes E or L, referring to “early” or “late” transcription events, although not all of those designated “early” are actually transcribed early, and vice versa.
Descriptions of certain primers and oligonucleotide probes for the detection of the E6 region of HPV types 16 and 18 are provided in Lucotte at al., Mol. Cell. Probes 7:339-344, 1993; De Britton et al., Obst. Gynec. 81:19-24, 1993; Nuevo, at al., Am. J. Pathol. 138:53-58, 1991; Van der Velde et al., J. Med. Virol. 36:279-282, 1992; Thompson et al., J. Med. Viral. 36:54-6, 1992; Cornelissen et at, J. Gen. Virol. 71:1243-1246, 1990, Hus and McNicol, Mol. Cell. Probes 6:459-466, 1992; Sang and Barbosa, Virol. 189:448-465, 1992; Joseph, European Pub. No. 0 477 972; Joannes et al., PCT Pub. No. WO 93/02217; Emery et al., PCT Pub. No. WO 92/01816; Hendricks, POT Pub. No. WO 91/08312, PCT Pub. No. PCT/US90/07057; Manos et al., U.S. Pat. No. 5,182,377; Herzog, et al., U.S. Pat. No. 4,983,728; Schwartz and Adams, PCT Pub. No. WO 89/02934; George and Groff, PCT Pub. No. WO 89/09940; Nur at al., PCT Pub. No. WO 92/14847; Mazzatente et al., European Pat. Pub. No. EPO 489 442; Shimada et al., European Pat. Pub. No. EPO 402 132; and Morris et al., PCT Pub. No. WO 88/06634; all of which are hereby incorporated herein by reference in their entirety (including drawings).